Tacrolimus and Mycophenolate Mofetil in Preventing Graft-Versus-Host Disease in Patients Who Have Undergone Total-Body Irradiation With or Without Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant for Hematologic Cancer

This phase II trial studies how well tacrolimus and mycophenolate mofetil works in preventing graft-versus-host disease in patients who have undergone total-body irradiation (TBI) with or without fludarabine phosphate followed by donor peripheral blood stem cell transplant for hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, and TBI before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening.

A Multi-Center Study of Nonmyeloablative Conditioning With TBI or Fludarabine/TBI for HLA-matched Related Hematopoietic Cell Transplantation for Treatment of Hematologic Malignancies With Post Grafting Immunosuppression With Tacrolimus and Mycophenolate Mofetil

Experimental: Arm I (nonmyeloablative conditioning with fludarabine and TBI)

Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

Drug: fludarabine phosphate

Given IV

Other Names:

2-F-ara-AMP

Beneflur

Fludara

Radiation: total-body irradiation

Undergo radiotherapy

Other Name: TBI

Other: laboratory biomarker analysis

Correlative studies

Experimental: Arm II (nonmyeloablative conditioning with TBI)

Patients undergo TBI on day 0. All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus PO every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO.

All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus orally (PO) every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 3 years.

Eligibility

Ages Eligible for Study:

up to 74 Years (Child, Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patient must be not eligible for conventional allogeneic hematopoietic cell transplantation (HCT) and must have disease expected to be stable for at least 100 days without chemotherapy; patients with hematologic malignancies treatable with HCT or with a B cell malignancy except those curable with autologous transplant will be included; patients not eligible for active disease specific protocols may be enrolled in this protocol; patients will include the following

Diffuse large B cell non-Hodgkin lymphoma (NHL) and other aggressive lymphomas - not eligible for conventional myeloablative HCT or after autologous HCT

Chronic lymphocytic leukemia (CLL) - must have either 1) failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine phosphate (FLU) (or another nucleoside analog, e.g. 2-chlorodeoxyadenosine [2-CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog); 2) failed FLU-cyclophosphamide (CY)-Rituximab (FCR) combination chemotherapy at any time point; or 3) have "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st CR; 4) patients with a diagnosis of CLL (or small lymphocytic lymphoma) or a diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL

Hodgkin lymphoma (HL) - must have received and failed frontline therapy; patients must have failed or were not eligible for autologous transplant

Multiple myeloma (MM) - following a planned autologous transplant or equivalent high-dose therapy without a graft, or following a failed prior autograft

Acute myeloid leukemia (AML) - must have < 5% marrow blasts at the time of transplant

Acute lymphoblastic leukemia (ALL) - must have < 5% marrow blasts at the time of transplant

Chronic myelogenous leukemia (CML) - patients will be accepted beyond first chronic phase (CP1) if they have received previous myelosuppressive chemotherapy or HCT, and have < 5% marrow blasts at time of transplant

Myelodysplastic syndromes/myeloproliferative disorders (MDS/MPD) - must have received previous myelosuppressive chemotherapy or HCT, and have < 5% marrow blasts at time of transplant

Waldenstrom's macroglobulinemia - must have failed 2 courses of therapy

Myelosuppressive chemotherapy must be discontinued three weeks prior to conditioning with the exception of hydroxyurea or imatinib

Patients < 12 years old must be approved by both the participating institutions' patient review committee such as the Patient Care Conference (PCC) at the Fred Hutchinson Cancer Research Center (FHCRC) and the FHCRC principal investigator

Patient who refused to be treated on a conventional HCT protocol; for this inclusion criterion, transplants must be approved by both the participating institution's patient review committee such as the Patient Care Conference (PCC) at the FHCRC and the FHCRC principal investigators

Patients with human leukocyte antigen (HLA)-matched related donors

Patients with renal failure are eligible; however, patients with renal compromise (serum creatinine > 2.0) will likely have further compromise in renal function and may require hemodialysis (which may be permanent) due to the need to maintain adequate serum tacrolimus levels

DONOR: Related donor who is HLA genotypically identical at least at one haplotype and may be phenotypically or genotypically identical at the allele level at HLA-A, -B, -C, -DRB1, and -DQB1

DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis

DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)

Any current central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy

Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, ALL or CML

Fertile men or women unwilling to use contraceptives during and for up to 12 months post treatment

Female patients who are pregnant or breastfeeding

Human immunodeficiency virus (HIV)-positive patients

Patients with active non-hematologic malignancies (except non-melanoma skin cancers); this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy

Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy

Fungal pneumonia with radiological progression after receipt of amphotericin formulation or mold-active azoles for greater than 1 month

Karnofsky score < 50 for adult patients

Lansky-Play performance score < 50 for pediatric patients

Symptomatic coronary artery disease or ejection fraction < 35% or other cardiac failure requiring therapy (or, if unable to obtain ejection fraction, shortening fraction of < 26%); ejection fraction is required if age > 50 years or there is a history of anthracycline exposure or history of cardiac disease; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist

Liver function abnormalities: Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease

DONOR: Current serious systemic illness that would result in increased risk for G-CSF mobilization and harvest of peripheral blood stem cells (PBSC)

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00089011